dc.contributor.author | Cox, Rebecca Jane | en_US |
dc.contributor.author | Major, Diane | en_US |
dc.contributor.author | Pedersen, Gabriel Kristian | en_US |
dc.contributor.author | Pathirana, Rishi | en_US |
dc.contributor.author | Höschler, Katja | en_US |
dc.contributor.author | Guilfoyle, Kate | en_US |
dc.contributor.author | Roseby, Sarah | en_US |
dc.contributor.author | Bredholt, Geir | en_US |
dc.contributor.author | Assmus, Jörg | en_US |
dc.contributor.author | Breakwell, Lucy | en_US |
dc.contributor.author | Campitelli, Laura | en_US |
dc.contributor.author | Sjursen, Haakon | en_US |
dc.date.accessioned | 2016-01-11T13:52:02Z | |
dc.date.available | 2016-01-11T13:52:02Z | |
dc.date.issued | 2015-07-06 | |
dc.Published | PLoS ONE 2015, 10:e0131652(7) | eng |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | https://hdl.handle.net/1956/10924 | |
dc.description.abstract | Background and Methods: Highly pathogenic avian influenza (HPAI) viruses constitute a pandemic threat and the development of effective vaccines is a global priority. Sixty adults were recruited into a randomized clinical trial and were intramuscularly immunized with two virosomal vaccine H5N1 (NIBRG-14) doses (21 days apart) of 30μg HA alone or 1.5, 7.5 or 30μg HA adjuvanted with Matrix M. The kinetics and longevity of the serological responses against NIBRG-14 were determined by haemagglutination inhibition (HI), single radial haemolysis (SRH), microneutralization (MN) and ELISA assays. The cross-H5 clade responses in sera were determined by HI and the antibody-secreting (ASC) cell ELISPOT assays. The protective efficacy of the vaccine against homologous HPAI challenge was evaluated in ferrets. Results: The serological responses against the homologous and cross-reactive strains generally peaked one week after the second dose, and formulation with Matrix M augmented the responses. The NIBRG-14-specific seroprotection rates fell significantly by six months and were low against cross-reactive strains although the adjuvant appeared to prolong the longevity of the protective responses in some subjects. By 12 months post-vaccination, nearly all vaccinees had NIBRG-14-specific antibody titres below the protective thresholds. The Matrix M adjuvant was shown to greatly improve ASC and serum IgG responses following vaccination. In a HPAI ferret challenge model, the vaccine protected the animals from febrile responses, severe weight loss and local and systemic spread of the virus. Conclusion: Our findings show that the Matrix M-adjuvanted virosomal H5N1 vaccine is a promising pre-pandemic vaccine candidate. | en_US |
dc.language.iso | eng | eng |
dc.publisher | PLOS | eng |
dc.rights | Attribution CC BY 4.0 | eng |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0 | eng |
dc.subject | Vaccines | eng |
dc.subject | H5N1 | eng |
dc.title | Matrix M H5N1 vaccine induces cross-H5 clade humoral immune responses in a randomized clinical trial and provides protection from highly pathogenic influenza challenge in ferrets | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2015-12-22T10:38:18Z | |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2015 Cox et al. | |
dc.identifier.doi | https://doi.org/10.1371/journal.pone.0131652 | |
dc.identifier.cristin | 1283979 | |
dc.relation.project | Norges forskningsråd: 220670 | |
dc.subject.nsi | VDP::Medisinske Fag: 700 | en_US |